WO2008071081A8 - Préparation d'une protéine hybride anticoagulante provoquant un faible saignement et utilisation de cette dernière - Google Patents

Préparation d'une protéine hybride anticoagulante provoquant un faible saignement et utilisation de cette dernière Download PDF

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Publication number
WO2008071081A8
WO2008071081A8 PCT/CN2007/003526 CN2007003526W WO2008071081A8 WO 2008071081 A8 WO2008071081 A8 WO 2008071081A8 CN 2007003526 W CN2007003526 W CN 2007003526W WO 2008071081 A8 WO2008071081 A8 WO 2008071081A8
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WO
WIPO (PCT)
Prior art keywords
fusion protein
preparation
low bleeding
anticoagulant fusion
anticoagulant
Prior art date
Application number
PCT/CN2007/003526
Other languages
English (en)
Chinese (zh)
Other versions
WO2008071081A1 (fr
Inventor
Zuze Wu
Aiping Yu
Chuanling Zhang
Zhongxiong Tang
Original Assignee
Inst Radiation Med Amms Pla
Beijing Sanly Sci Tech Develop
Zuze Wu
Aiping Yu
Chuanling Zhang
Zhongxiong Tang
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Inst Radiation Med Amms Pla, Beijing Sanly Sci Tech Develop, Zuze Wu, Aiping Yu, Chuanling Zhang, Zhongxiong Tang filed Critical Inst Radiation Med Amms Pla
Priority to EP07845883A priority Critical patent/EP2103630B1/fr
Priority to US12/519,309 priority patent/US8101379B2/en
Priority to CN2007800463406A priority patent/CN101668778B/zh
Priority to AT07845883T priority patent/ATE533789T1/de
Priority to JP2009540580A priority patent/JP5345069B2/ja
Publication of WO2008071081A1 publication Critical patent/WO2008071081A1/fr
Publication of WO2008071081A8 publication Critical patent/WO2008071081A8/fr

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711Alzheimer's disease; Amyloid plaque core protein
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81Protease inhibitors
    • C07K14/8107Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121Serpins
    • C07K14/8128Antithrombin III
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81Protease inhibitors
    • C07K14/815Protease inhibitors from leeches, e.g. hirudin, eglin
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6432Coagulation factor Xa (3.4.21.6)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6443Coagulation factor XIa (3.4.21.27)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21006Coagulation factor Xa (3.4.21.6)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21027Coagulation factor XIa (3.4.21.27)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Microbiology (AREA)
  • Toxicology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Neurology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne une protéine hybride anticoagulante qui comprend un oligopeptide reconnu et clivé soit par le facteur XIa et le facteur Xa soit par la thrombine et le facteur Xa. Cette invention concerne également le procédé de préparation de la protéine hybride anticoagulante et l'utilisation médicinale de cette dernière.
PCT/CN2007/003526 2006-12-15 2007-12-11 Préparation d'une protéine hybride anticoagulante provoquant un faible saignement et utilisation de cette dernière WO2008071081A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP07845883A EP2103630B1 (fr) 2006-12-15 2007-12-11 Préparation d'une protéine hybride anticoagulante provoquant un faible saignement et utilisation de cette dernière
US12/519,309 US8101379B2 (en) 2006-12-15 2007-12-11 Preparation of low bleeding anticoagulant fusion protein and its use
CN2007800463406A CN101668778B (zh) 2006-12-15 2007-12-11 低出血抗凝血融合蛋白的制备及其应用
AT07845883T ATE533789T1 (de) 2006-12-15 2007-12-11 Herstellung von mit geringen blutungen assoziiertem gerinnungshemmendem fusionsprotein und dessen verwendung
JP2009540580A JP5345069B2 (ja) 2006-12-15 2007-12-11 低出血性抗凝固性融合タンパク質の調製および使用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200610165756 2006-12-15
CN200610165756.7 2006-12-15

Publications (2)

Publication Number Publication Date
WO2008071081A1 WO2008071081A1 (fr) 2008-06-19
WO2008071081A8 true WO2008071081A8 (fr) 2009-08-13

Family

ID=39511252

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2007/003526 WO2008071081A1 (fr) 2006-12-15 2007-12-11 Préparation d'une protéine hybride anticoagulante provoquant un faible saignement et utilisation de cette dernière

Country Status (6)

Country Link
US (1) US8101379B2 (fr)
EP (1) EP2103630B1 (fr)
JP (1) JP5345069B2 (fr)
CN (1) CN101668778B (fr)
AT (1) ATE533789T1 (fr)
WO (1) WO2008071081A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006045503A1 (fr) 2004-10-19 2006-05-04 Lonza Ag Procede de synthese de peptides en phase solide
CN102180973B (zh) * 2011-03-18 2012-08-29 重庆大学 靶向多功能防栓融合蛋白及其制备方法和应用
CN109206522B (zh) * 2017-07-07 2021-11-09 北京三有利和泽生物科技有限公司 一种长效抗凝血融合蛋白及其应用
CN115572329B (zh) * 2021-06-21 2024-02-06 王大勇 一组活性增强代谢较慢的菲牛蛭基因重组水蛭素及其制备方法
CN113956339B (zh) * 2021-10-28 2023-02-24 中国药科大学 宽体金线蛭抗凝血因子XIa多肽及其应用

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5759542A (en) * 1994-08-05 1998-06-02 New England Deaconess Hospital Corporation Compositions and methods for the delivery of drugs by platelets for the treatment of cardiovascular and other diseases
PT833848E (pt) * 1995-06-12 2002-01-30 Sanquin Bloedvoorziening Peptidos ligantes do factor ix derivados do factor viii e sua utilizacao como inibidores da coagulacao do sangue
US5910481A (en) * 1995-11-13 1999-06-08 Immuno Ag Hybrid proteins with modified activity
CN1480466A (zh) * 2002-09-03 2004-03-10 �й������ž�����ҽѧ��ѧԺ����ҽ 一类溶栓抗凝双功能融合蛋白及应用
CN1896108B (zh) * 2005-06-01 2012-01-04 中国人民解放军军事医学科学院放射与辐射医学研究所 特异性抗凝血物质的制备及其应用

Also Published As

Publication number Publication date
CN101668778B (zh) 2012-10-03
CN101668778A (zh) 2010-03-10
US20100113345A1 (en) 2010-05-06
JP5345069B2 (ja) 2013-11-20
EP2103630A1 (fr) 2009-09-23
JP2010512349A (ja) 2010-04-22
EP2103630A4 (fr) 2010-07-28
EP2103630B1 (fr) 2011-11-16
US20100234291A2 (en) 2010-09-16
US8101379B2 (en) 2012-01-24
ATE533789T1 (de) 2011-12-15
WO2008071081A1 (fr) 2008-06-19

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